The approaches outlined in Part I suggest new routes to obtaining homogeneous complexes of CD4 and HIV gp120. Crystallization of these complexes, which involve the two-domain fragment CD4 (1-183) and various deglycosylate and truncated derivatives of gp120, will be attempted. The goal is determination of a three-dimensional structure of the CD4/gp120 complex by X-ray diffraction to whatever resolution the crystals will afford. Further knowledge of the structure of this complex will be important for design of compounds that block viral attachment or that inactivate HIV by mimicking CD4. In addition, efforts will be made to determine the structure of complexes of CD4 (1-183) with compounds already available that interfere with the CD4/gp120 interaction. Two strategies will be attempted: co-crystallization of the compounds with CD4(1-183), and diffusion of the compounds into CD4(1-183)/Fab co- crystals. The determination of one or more such structures will permit more rational design of actual drug candidates.